PMID- 27015224
OWN - NLM
STAT- MEDLINE
DCOM- 20160803
LR  - 20210109
IS  - 1536-5964 (Electronic)
IS  - 0025-7974 (Print)
IS  - 0025-7974 (Linking)
VI  - 95
IP  - 12
DP  - 2016 Mar
TI  - Combination With Low-dose Dextromethorphan Improves the Effect of Amlodipine 
      Monotherapy in Clinical Hypertension: A First-in-human, Concept-proven, 
      Prospective, Dose-escalation, Multicenter Study.
PG  - e3234
LID - 10.1097/MD.0000000000003234 [doi]
LID - e3234
AB  - The combination of low rather than high dose of dextromethorphan (DXM) with 
      amlodipine (AM) could improve blood pressure (BP) reduction in hypertensive 
      animals. The study aimed to evaluate the feasibility of different doses of DXM 
      combined with standard AM treatment in clinical hypertension.This was a 
      prospective, 14-week, dose-escalation, multicenter study. After 2-week run-in 
      period with AM 5 mg/day, hypertensive patients who got the BP goal of 140/90 mmHg 
      kept receiving AM monotherapy for another 12 weeks. The nonresponders, while kept 
      on AM 5 mg/day, received additional DXM treatment for 3 sequential dose-titrated 
      periods with initially 2.5 mg/day, followed by 7.5 mg/day, and finally 30 mg/day. 
      Each period was for 4 weeks. The patients at BP goal after each treatment period 
      were defined as the responders and kept on the same combination till the end of 
      the study. The responder rate of each treatment period was recorded. The changes 
      of BP and serum antioxidant/endothelial markers between week 14 and week 2 were 
      evaluated.Of the 103 patients initially enrolled, 89 entered the treatment 
      period. In the 78 patients completing the study, 31 (40%) at BP goal after 2-week 
      AM run-in kept on AM monotherapy (DXM0). The addition of 2.5 (DXM2.5) and 
      7.5 mg/day (DXM7.5) of DXM enabled BP goal achievement in 22 (47%) nonresponders 
      to AM monotherapy including 16 (29%) with DXM2.5 and 6 (18%) with DXM7.5. Only 4 
      patients (16%) reached BP goal with the combination of DXM 30 mg/day (DXM30). 
      Overall, 73% of the 78 patients reached BP goal at the end of the 14-week study. 
      Mean systolic BP was reduced by 7.9% +/- 7.0% with DXM2.5 (P < 0.001) and by 
      5.4% +/- 2.4% with DXM7.5 (P = 0.003) respectively at week 14 from that at week 2, 
      which was unchanged in either DXM0 or DXM30 group. Besides, the effects of 
      combination treatment were particularly significant in the patients with impaired 
      endothelial function suggested by reduced serum NOx level at 
      baseline.Accordingly, the combination with low dose of DXM was feasible to 
      improve BP control in patients who failed to achieve the BP goal by standard AM 
      monotherapy. The benefit effects might be significant especially in patients with 
      impaired endothelial function.
FAU - Yin, Wei-Hsian
AU  - Yin WH
AD  - From the Heart Center, Cheng-Hsin General Hospital (W-HY); Faculty of Medicine, 
      National Yang-Ming University (W-HY); Institute of Pharmacology, National 
      Yang-Ming University (J-WC); TSH Biopharm Corporation Ltd (PC); Department of 
      Medicine, Mackay Memorial Hospital, Taipei (H-IY); Division of Cardiology, 
      Taichung Veterans General Hospital (K-YW); Department of Internal Medicine, Chung 
      San Medical University, Taichung (K-YW); Division of Endocrinology and Metabolism 
      (Y-JH); Division of Cardiology, Tri-Service General Hospital, Taipei (S-MC); 
      Department of Cardiology, E-DA Medical University Hospital, Kaohsiung (W-KT); 
      Department of Cardiology, Chang Gung Memorial Hospital Linkou, Taoyuan (M-SW); 
      Division of Cardiology, Taipei Veterans General Hospital (T-CW, J-WC); Department 
      of Internal Medicine, National Taiwan University Hospital (C-CW); and Department 
      of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC 
      (J-WC).
FAU - Chen, Pei
AU  - Chen P
FAU - Yeh, Hung-I
AU  - Yeh HI
FAU - Wang, Kuo-Yang
AU  - Wang KY
FAU - Hung, Yi-Jen
AU  - Hung YJ
FAU - Tseng, Wei-Kung
AU  - Tseng WK
FAU - Wen, Ming-Shien
AU  - Wen MS
FAU - Wu, Tao-Cheng
AU  - Wu TC
FAU - Wu, Chau-Chung
AU  - Wu CC
FAU - Cheng, Shu-Meng
AU  - Cheng SM
FAU - Chen, Jaw-Wen
AU  - Chen JW
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Medicine (Baltimore)
JT  - Medicine
JID - 2985248R
RN  - 0 (Antihypertensive Agents)
RN  - 1J444QC288 (Amlodipine)
RN  - 7355X3ROTS (Dextromethorphan)
SB  - IM
MH  - Amlodipine/*administration & dosage
MH  - Antihypertensive Agents/*administration & dosage
MH  - Dextromethorphan/*administration & dosage
MH  - Drug Therapy, Combination
MH  - Female
MH  - Humans
MH  - Hypertension/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Prospective Studies
MH  - Single-Blind Method
PMC - PMC4998419
COIS- The authors report no conflicts of interest.
EDAT- 2016/03/26 06:00
MHDA- 2016/08/04 06:00
PMCR- 2016/03/25
CRDT- 2016/03/26 06:00
PHST- 2016/03/26 06:00 [entrez]
PHST- 2016/03/26 06:00 [pubmed]
PHST- 2016/08/04 06:00 [medline]
PHST- 2016/03/25 00:00 [pmc-release]
AID - 00005792-201603220-00061 [pii]
AID - 10.1097/MD.0000000000003234 [doi]
PST - ppublish
SO  - Medicine (Baltimore). 2016 Mar;95(12):e3234. doi: 10.1097/MD.0000000000003234.